Translational Medical Research Commons^™

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Regulation Of Oxidative Phosphorylation Of Liver Mitochondria In Sepsis, Pierre Eyenga, Benjamin Rey, Lilia Eyenga, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

The link between liver dysfunction and decreased mitochondrial oxidative phosphorylation in sepsis has been clearly established in experimental models. Energy transduction is plastic: the efficiency of mitochondrial coupling collapses in the early stage of sepsis but is expected to increase during the recovery phases of sepsis. Among the mechanisms regulating the coupling efficiency of hepatic mitochondria, the slipping reactions at the cytochrome oxidase and ATP synthase seem to be a determining element, whereas other regulatory mechanisms such as those involving proton leakage across the mitochondrial membrane have not yet been formally proven in the context of sepsis. If the dysfunction …

The Effect Of Medical Nutrition Therapy On Weight Loss, Ayesha Baig, Hannah Kostan, Cynthia Cheng

Phase 1

Introduction: In this retrospective study, we evaluated the effects of Jefferson’s medical nutrition therapy (MNT) program on weight loss. We anticipate that participation in the MNT program will lead to an improvement in weight and metabolic syndrome parameters.

Methods: We selected a convenience sample of 10 participants with BMI > 25 for this pilot retrospective chart review. Subjects were screened for various exclusion criteria such as past bariatric surgery, heart failure, malignancy, renal dialysis, and uncontrolled conditions such as hypothyroidism, anemia, or B12 deficiency. Weight measurements were collected from EPIC records starting from baseline, defined as 3 months prior to initiation …

Diagnostic Accuracy Of Procalcitonin In Differentiating Sepsis From Noninfectious Sirs In Adult Patients With Subarachnoid Hemorrhage, Keshav Choudhuri, Umer Mukhtar, Md, M. Kamran Athar, Md, David Boorman, Ms, Fred Rincon, Md, Matthew Vibbert, Md, Syed O. Shah, Md, Jacqueline S. Urtecho, Md, Jack Jallo, Md

Phase 1

Background: Subarachnoid hemorrhage (SAH) is a frequent diagnosis in the neuro-intensive care unit (NICU) that can result in the development of systemic inflammatory response syndrome (SIRS) and fever. The differentiation between central fever and infectious fever is paramount in order to prevent superfluous diagnostic testing and overuse of empiric antibiotics.

Methods: A prospective chart review study conducted in the NICU between December 2012 and September 2015. Patients with SAH, fever (≥101.0°F) and/or who were SIRS positive and had PCT levels measured were included. The primary outcome was clinical infection defined as any positive culture or infiltrate on chest X-ray within …

A Continuum Of Disease From Community-Acquired Pneumonia To Multiple Organ Dysfunction Syndrome, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Ticagrelor Reduces Thromboinflammatory Markers In Patients With Pneumonia, Travis R. Sexton, Guoying Zhang, Tracy E. Macaulay, Leigh Ann Callahan, Richard Charnigo, Olga A. Vsevolozhskaya, Zhenyu Li, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y₁₂ receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches …

Reducing Sepsis Mortality: A Cloud-Based Alert Approach, Janet A. Zink

Theses and Dissertations

The aim of this study is to examine the impact of a cloud-based CDS alerting system for SIRS, a precursor to sepsis, and sepsis itself, on adult patient and process outcomes at VCU Health System. The two main hypotheses are: 1) the implementation of cloud-based SIRS and sepsis alerts will lead to lower sepsis-related mortality and lower average length of stay, and 2) the implementation of cloud-based SIRS and sepsis alerts will lead to more frequent ordering of the Sepsis PowerPlan and more recording of sepsis diagnoses. To measure these outcomes, a pre-post study was conducted. A pre-implementation group diagnosed …

New Insights Into Post-Sepsis Muscle Weakness Elucidated Using A Novel Animal Model, Allison M. Steele

Theses and Dissertations--Physiology

Sepsis is a severe life-threatening critical illness that damages multiple physiological systems. After hospital discharge, more than 70% of severe sepsis survivors report profound weakness which significantly impacts quality of life. Such weakness gives rise to new limitations of daily living, which ultimately leads to loss of independence in many patients. Despite wide recognition of this serious issue by clinicians and researchers alike, the mechanisms contributing to chronic skeletal muscle dysfunction after sepsis are not well understood. Lack of progress in this field is largely due to the absence of an appropriate animal model; current models are either too mild …